Maternal Psychiatric Illness, Treatment with SSRIs, and Autism Spectrum Disorders (ASD)

Background: Depression and its treatment with antidepressants have increased over the past two decades. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to manage depression during pregnancy. Evidence from several human studies indicates that prenatal exposure to SSRIs may increase the risk of ASD in the offspring. However, whether the treatment itself, or the underlying indication for treatment, i.e. – the psychiatric disorder, is the etiologically relevant factor remains to be clarified.

Objectives: To investigate history of maternal psychiatric illness, maternal treatment with SSRIs during pregnancy, and their association with risk of ASD in the offspring.

Methods: The study population was drawn from the Study to Explore Early Development, a multi-site case-control study conducted in six sites across the United States among children born between 2003-2011. Children were enrolled at 2-5 years of age. Final study group classification (ASD, developmental delay (DD), general population control (POP)) was determined by an in-person standardized developmental assessment. Maternal history of psychiatric disorders and use of antidepressants during pregnancy were ascertained in three ways: maternal telephone interview shortly after study enrollment, self-report on maternal medical history form, and review of maternal medical records. During the interview, the mother was also asked to specify type of psychiatric illness and date of onset, and types and timing of antidepressant medications taken during pregnancy. To evaluate the independent and multiplicative effects of maternal psychiatric illness and treatment with SSRIs on ASD risk (vs. POP), three separate logistic regression models were run by trimester of exposure: 1) independent effect of psychiatric illness: maternal psychiatric illness but no treatment (Psy-Yes + SSRI-No) vs. no illness and no treatment (Psy-No + SSRI-No); 2) independent treatment effect: psychiatric illness and SSRI use (Psy-Yes + SSRI-Yes) vs. psychiatric illness but no SSRI use (Psy-Yes + SSRI-No; 3) combined effect: psychiatric illness and SSRI use (Psy-Yes + SSRI-Yes) vs. no psychiatric illness and no SSRI use (Psy-No + SSRI-No). Covariates in adjusted analyses included maternal race, education, age at delivery, history of smoking, and household income during pregnancy.

Results: Maternal history of any psychiatric illness prior to the delivery of the study child (36% vs. 27%) and antidepressant use during pregnancy (10.8% vs. 7.2%) were significantly more common among the mothers of ASD cases (N=1367) than POP controls (N=1671). The adjusted odds of having a child with ASD were ~80% higher among women with a history of psychiatric illness independent of SSRI use (Psy-Yes + SSRI-No vs. Psy-No + SSRI-No: OR=1.81, 95% CI 1.44-2.27). The odds of ASD were not higher among children prenatally exposed to SSRIs independent of maternal history of psychiatric illness (Psy-Yes + SSRI-Yes vs. Psy-Yes + SSRI-No: OR=1.14, 95% CI 0.8-1.62). Children with both exposures had a doubling in odds of ASD compared with children with neither exposure (Psy Yes + SSRI Yes vs. Psy-No + SSRI-No: OR=2.0, 95% CI 1.5-2.8). Results did not differ by child sex.

Conclusions: We found no evidence that prenatal exposure to SSRIs is associated with increased risk of ASD independent of indication for treatment.